Basic Mechanisms of DNA-Raised Antibody Responses to Intramuscular and Gene Gun Immunizations

Boyle, Christine M.; Robinson, Harriet L.
March 2000
DNA & Cell Biology;Mar2000, Vol. 19 Issue 3, p157
Academic Journal
DNA-raised antibody (Ab) responses have been compared for the dependence on CD4 + and CD8 + cells, the longevity of functional antigen (Ag) expression, and the nature of the Ag-presenting cell after intramuscular (IM) and gene gun inoculations. A plasmid expressing the hemagglutinin (HA) glycoprotein of influenza virus was used for immunizations of BALB/c mice. Intramuscular and gene gun-raised Abs had similar dependencies on CD4 + and CD8 + cells but different temporal patterns of functional Ag expression. The two methods of DNA immunization also appeared to have different frequencies or types of Ag-presenting cells in the draining lymph nodes and spleen. For both methods of DNA delivery, Ab was independent of CD8 + cells but dependent on CD4 + cells. The CD4 dependence occurred at priming but not booster immunizations and resulted in a 1-month delay in the Ab response. Temporal T-cell transfers from TCR +/+ mice into immunized TCR -/- mice revealed the persistence of DNA-expressed Ag for up to 1 month after both IM and gene gun inoculations. For gene gun, but not IM immunizations, approximately 90% of the functional Ag expression was lost by 1 week, consistent with the sloughing of the epidermal target site. Despite similar titers of raised Ab, Ag-presenting dendritic cells could be detected in the draining lymph nodes and spleen of gene gun- but not IM DNA-immunized mice. In the gene gun-immunized mice, Ag-presenting dendritic cells appeared in the draining lymph nodes before the spleen.


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